Effect of Electric Field on α-Synuclein Fibrils: Revealed by Molecular Dynamics Simulations

Jamoliddin Razzokov, Sunnatullo Fazliev, Mukhriddin Makhkamov, Parthiban Marimuthu, Artyom Baev, Erkin Kurganov

Research output: Contribution to journalArticleScientificpeer-review

4 Citations (Scopus)
19 Downloads (Pure)

Abstract

The self-association of amylogenic proteins to the fibril form is considered a pivotal factor in the pathogenesis of neurodegenerative diseases, including Parkinson's disease (PD). PD causes unintended or uncontrollable movements in its common symptoms. α-synuclein is the major cause of PD development and thus has been the main target of numerous studies to suppress and sequester its expression or effectively degrade it. Nonetheless, to date, there are no efficient and proven ways to prevent pathological protein aggregation. Recent investigations proposed applying an external electric field to interrupt the fibrils. This method is a non-invasive approach that has a certain benefit over others. We performed molecular dynamics (MD) simulations by applying an electric field on highly toxic fibrils of α-synuclein to gain a molecular-level insight into fibril disruption mechanisms. The results revealed that the applied external electric field induces substantial changes in the conformation of the α-synuclein fibrils. Furthermore, we show the threshold value for electric field strength required to completely disrupt the α-synuclein fibrils by opening the hydrophobic core of the fibril. Thus, our findings might serve as a valuable foundation to better understand molecular-level mechanisms of the α-synuclein fibrils disaggregation process under an applied external electric field.

Original languageEnglish
Article number6312
Number of pages11
JournalInternational Journal of Molecular Sciences
Volume24
Issue number7
DOIs
Publication statusPublished - 28 Mar 2023
MoE publication typeA1 Journal article-refereed

Keywords

  • Humans
  • alpha-Synuclein/metabolism
  • Molecular Dynamics Simulation
  • Parkinson Disease/metabolism
  • Protein Aggregation, Pathological/complications
  • Amyloid/metabolism

Fingerprint

Dive into the research topics of 'Effect of Electric Field on α-Synuclein Fibrils: Revealed by Molecular Dynamics Simulations'. Together they form a unique fingerprint.

Cite this